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The mass start event is the longest cross-country skiing event added first time in the Pyeongchang Winter Olympics held in 2018. This study aimed to highlight tactics characteristics of the event by making a statistical analysis of the points and competition results of athletes who participated in this event in the Pyeongchang Winter Olympics. For this purpose, the ranks, points, lap time, and final results of 16 male and 16 female athletes were taken as research objects in the final mass- start event of speed skating of the 2018 Pyeongchang Winter Olympics. The speed and speed coefficient of this segment were calculated by Pearson correlation analysis applying the Origin 9.4 software for nonlinear curve fitting. The results showed that athletes adopted different speed pacing strategies in each race. The analysis was based on a comparison of points and speed rhythms of different rounds. This enabled to identify and optimize tactics that might improve the probability of winning the event. This study contributes significantly with both theoretical and practical implications. The study findings specify such optimization tactics to provide a theoretical basis for sports practices as well as giving practical insights important to practitioners and sports officials. The study recommends that physical fitness should be strengthened to ensure athletes' speed endurance in speed-skating; teammates should work together tactically to get rid of the impact caused by physical exertion, and a training platform should be built to train athletes. [ABSTRACT FROM AUTHOR]

Background: Tumor progression following endocrine therapy is considered to indicate resistance to endocrine drugs due to a variety of mechanisms. An insufficient dose of endocrine drugs is one of the causes for treatment failure in some patients with high hormone-receptor (HR)-expressing advanced breast cancer. This study aimed to explore the efficacy of high-dose tamoxifen (TAM) treatment in patients with advanced breast cancer with highly expressed HR. Materials & methods: This was a single-arm, phase II pilot study that enrolled patients with advanced breast cancer with high HR expression (estrogen receptor ⩾60% and/or progesterone receptor ⩾60%) following routine endocrine therapy. All enrolled patients received a high-dose of TAM (100 mg/day) until disease progression. The primary endpoint was progression-free survival (PFS). The secondary endpoints included objective response rate (ORR), clinical benefit rate (CBR), overall survival (OS), and safety. Exploratory endpoints included the predictive value of 16α-18F-17β-fluoroestradiol quantitative positron emission tomography/computed tomography (18F-FES PET/CT) for treatment efficacy. Results: A total of 30 patients were enrolled between September 2017 and February 2019. The median PFS was 6 months [95% confidence interval (CI) 4.9–7.1] and the median OS was 15.6 months (95% CI 8.3–22.9). Five patients experienced a partial response (PR) and none experienced a complete response (CR), with an ORR of 16.7% and CBR of 33.3%. No severe adverse events were observed. Lesions with 18F-FES maximum standardized uptake value (SUVmax) ⩾4 had a significantly longer PFS [median 9.2 months, (95% CI 6.9–11.6)] compared with lesions with a 18F-FES SUVmax <4 [median 4.8 months, (95% CI 3.9–5.6); p = 0.022]. Conclusion: A high-dose of TAM is effective and safe for patients with advanced breast cancer with high HR expression. 18F-FES SUVmax values may predict the local clinical benefits of high-dose TAM. Trial Registration: [ClinicalTrials.gov identifier: NCT0304565] [ABSTRACT FROM AUTHOR]

Background: Taxane-induced peripheral neuropathy (TIPN) is a dose-limiting adverse effect. Ganglioside-monosialic acid (GM1) functions as a neuroprotective factor. We assessed the effects of GM1 on the prevention of TIPN in breast cancer patients.Methods: We conducted a randomized, double-blind, placebo-controlled trial including 206 patients with early-stage breast cancer planning to receive taxane-based adjuvant chemotherapy with a follow-up of more than 1 year. Subjects were randomly assigned to receive GM1 (80 mg, day -1 to day 2) or placebo. The primary endpoint was the Functional Assessment of Cancer Treatment Neurotoxicity subscale score after four cycles of chemotherapy. Secondary endpoints included neurotoxicity evaluated by National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0 and the Eastern Cooperative Oncology Group neuropathy scale. All statistical tests were two-sided.Results: In 183 evaluable patients, the GM1 group reported better mean Functional Assessment of Cancer Treatment Neurotoxicity subscale scores than patients in the placebo group after four cycles of chemotherapy (43.27, 95% confidence interval [CI] = 43.05 to 43.49 vs 34.34, 95% CI = 33.78 to 34.89; mean difference = 8.96, 95% CI = 8.38 to 9.54, P < .001). Grade 1 or higher peripheral neurotoxicity in Common Terminology Criteria for Adverse Events v4.0 scale was statistically significantly lower in the GM1 group (14.3% vs 100.0%, P < .001). Additionally, the GM1 group had a statistically significantly lower incidence of grade 1 or higher neurotoxicity assessed by Eastern Cooperative Oncology Group neuropathy scale sensory neuropathy (26.4% vs 97.8%, P < .001) and motor neuropathy subscales (20.9% vs 81.5%, P < .001).Conclusions: The treatment with GM1 resulted in a reduction in the severity and incidence of TIPN after four cycles of taxane-containing chemotherapy in patients with breast cancer. [ABSTRACT FROM AUTHOR]

The migration is the key step for thymic T cells to enter circulation and then lymph nodes (LNs), essential for future immune surveillance. Although promoter-based transcriptional regulation through Foxo1, Klf2, Ccr7, and Sell regulates T-cell migration, it remains largely unexplored whether and how enhancers are involved in this process. Here we found that the conditional deletion of Med1, a component of the mediator complex and a mediator between enhancers and RNA polymerase II, caused a reduction of both CD4 + and CD8 + T cells in LNs, as well as a decrease of CD8 + T cells in the spleen. Importantly, Med1 deletion hindered the migration of thymic αβT cells into the circulation and then into LNs, accompanied by the downregulation of KLF2, CCR7, and CD62L. Mechanistically, Med1 promotes Klf2 transcription by facilitating Foxo1 binding to the Klf2 enhancer. Furthermore, forced expression of Klf2 rescued Ccr7 and Sell expression, as well as αβT-cell migration into LNs. Collectively, our study unveils a crucial role for Med1 in regulating the enhancer-based Foxo1-Klf2 transcriptional program and the migration of αβT cells into LNs, providing valuable insights into the molecular mechanisms underlying T-cell migration., (© 2024 Wiley‐VCH GmbH.)

Memory CD8 + T cells play an essential role in providing effective and lifelong protection against pathogens. Comprehensive transcriptional and epigenetic networks are involved in modulating memory T cell development, but the molecular regulations of CD8 + memory T cell formation and long-term persistence remain largely unknown. In this study, we show that zinc finger protein 335 (Zfp335) is indispensable for CD8 + T cell memory establishment and maintenance during acute infections. Mice with Zfp335 deletion in CD8 + T cells exhibit a significant reduction of memory T cells and memory precursor cells in the contraction phase. Zfp335 deficiency in CD8 + T cells resulted in decreased expression of memory featured genes Eomes and IL-2Rβ, leading to a loss of memory identity and an increase of apoptosis in response to IL-7 and IL-15. Mechanistically, Zfp335 directly binds to and regulates TCF-1, known to be critical for memory T cell development. Importantly, overexpression TCF-1 could rescue the defects in the survival of both CD8 + memory precursors and memory T cells caused by Zfp335 deficiency. Collectively, our findings reveal that Zfp335 serves as a novel transcriptional factor upstream of TCF-1 in regulating CD8 + T cell memory., (Copyright © 2022 by The American Association of Immunologists, Inc.)

Effector CD8 + T cells are crucial players in adaptive immunity for effective protection against invading pathogens. The regulatory mechanisms underlying CD8 + T cell effector differentiation are incompletely understood. In this study, we defined a critical role of mediator complex subunit 1 (Med1) in controlling effector CD8 + T cell differentiation and survival during acute bacterial infection. Mice with Med1 -deficient CD8 + T cells exhibited significantly impaired expansion with evidently reduced killer cell lectin-like receptor G1 + terminally differentiated and Ly6c + effector cell populations. Moreover, Med1 deficiency led to enhanced cell apoptosis and expression of multiple inhibitory receptors (programmed cell death 1, T cell Ig and mucin domain-containing-3, and T cell immunoreceptor with Ig and ITIM domains). RNA-sequencing analysis revealed that T-bet- and Zeb2-mediated transcriptional programs were impaired in Med1 -deficient CD8 + T cells. Overexpression of T-bet could rescue the differentiation and survival of Med1 -deficient CD8 + effector T cells. Mechanistically, the transcription factor C/EBPβ promoted T-bet expression through interacting with Med1 in effector T cells. Collectively, our findings revealed a novel role of Med1 in regulating effector CD8 + T cell differentiation and survival in response to bacterial infection., (Copyright © 2022 by The American Association of Immunologists, Inc.)